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Despite our understanding of actomyosin function in individual migrating cells, we know little about the mechanisms by which actomyosin drives collective cell movement in vertebrate embryos. The collective movements of convergent extension drive both global reorganization of the early embryo and local remodeling during organogenesis. We report here that planar cell polarity (PCP) proteins control convergent extension by exploiting an evolutionarily ancient function of the septin cytoskeleton. By directing septin-mediated compartmentalization of cortical actomyosin, PCP proteins coordinate the specific shortening of mesenchymal cell-cell contacts, which in turn powers cell interdigitation. These data illuminate the interface between developmental signaling systems and the fundamental machinery of cell behavior and should provide insights into the etiology of human birth defects, such as spina bifida and congenital kidney cysts.
Fig. 1 Myosin-mediated cell cortex tension is planar polarized in Xenopus mesoderm.
(A to A″) pMyoII immunostaining of notochord in vivo (scale bar indicates 20 μm). (B) Illustration defining t- and v-type junctions and vertex angle ϕ (gray, ϕ for v-junction; red, ϕ of t-junction). A, anterior; P, posterior; M; medial; L, lateral. (C) Normalized intensity of pMyoII, defined as intensity relative to the maximum (=100%) and minimum (=0%) raw intensity for each image (n = 177 for v and 221 for t; three embryos). (D) Average vertex position change after ablation. Error bars indicate SE. (E and F) Scatter plots showing correlation between tension and edge length (E) or vertex angle (F) (n = 84 for v and 24 for t; 54 embryos).
Fig. 2 Pulsed actin assembly at v-junctions during edge shortening.
(A) Mosaic expression of two colors of the actin biosensors utrophin-FP. (A′) Time-lapse after the junction in box A′. Two populations of actin are visible: bipolar lamellipodia (green, arrowheads) and actin at the v-junction (magenta, arrows). (B) Mean intensity of utrophin (Utr, pink line) at v-junctions during edge length shortening (black line). (C) Edge length change is correlated with increase of utrophin intensity (red) but not with reduction in utrophin intensity (blue) (n = 133 cycles; six explants).
Fig. 3 Sept7 compartmentalizes cortical actin dynamics.
(A) Quantification of the lateral spread of paGFP-Utr at a cell vertex or edge (fig. S10A) (*P < 0.05, **P < 0.001, ***P < 0.0001, n = 7 to 11 explants). (B) GFP-sept7 localization in explant. (B′) GFP-sept7 colocalizes with Utr–red fluorescent protein (RFP) at vertices. (C and C′) Utr-GFP normally localizes at vertices. (D and D′) Sept7 knockdown disrupts utrophin accumulation at the vertices. (E) Quantification of (C) and (D) (see also fig. S7B). Scale bar, 20 μm; error bars, SE.
Fig. 4 Sept7 controls planar polarization of cell cortex tension.
(A to A″) pMyoII immunostaining of notochord in Sept7 knockdown embryos (compare with Fig. 1A) (scale bar, 20 μm). (B and C) The normal differences in pMyoII or vertex shift after laser ablation between v- and t-junctions are lost in Sept7 morphants (Sept7-MO). For (B), n = 74 for v and 188 for t; three embryos. For (C), n = 50 for v and 28 for t; 39 explants. (D) Average vertex shift for all junctions is not changed after Sept7 knockdown but is significantly reduced by treatment with a myosin kinase inhibitor (for control, n = 108; for sept7-MO, n = 78; for ML-7, n = 36, 111 explants). n.s., not significant; error bars, SE.
Fig. 5 PCP signaling regulates Sept7 localization.
(A and A′) GFP-Sept7 localizes at vertices in control explants. (B and B′) Dominant negative dishevelled (Xdd1) promotes ectopic GFP-Sept7 localization along edges (arrowheads). (C) Quantification of GFP-Sept7 localization (control, n = 67 and six explants; Sept7-MO, n = 50 and six explants; scale bar, 20 μm) (see also fig. S7B).
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